Tobacco is a very important part of the culture and agricultural economy in Kentucky, and is grown in 119 of its 120 counties. It is also grown in other states and around world. Tobacco harvesting workers are exposed to nicotine from wet tobacco plants. Approximately 1-47% of exposed workers may develop green tobacco sickness (GTS) that can be so severe, requiring emergency medical treatment. GTS causes significant discomfort and lost productivity. Current preventive measures using protective clothing or work schedule change may not be feasible and practical due to field limitations. New strategies for exposure control are needed. Barrier creams are often used in the workplace as an effective tool together with other protective methods to reduce exposure to chemicals. However, no nicotine barrier cream products are currently available. We propose to develop such a barrier cream and test it in vitro and in Kentucky tobacco farm workers. Nicotine in tobacco exists as a lipophilic free base and readily penetrates the skin. Nicotine forms a water-soluble salt with organic acids which we hypothesize may significantly lower its permeation through the skin and absorption into the blood. Our specific aims are: 1) to develop a nicotine barrier cream and identify optimal formulations in the laboratory; 2) to assess its efficacy in reducing dermal absorption of nicotine using in vitro testing; 3) evaluate its efficacy, acceptance, side effects ad feasibility in a field pilot study. Our approaches include: 1) develop barrier cream formulations and cleaning towelettes; 2) conduct in vitro testing to identify optimal formulations; 3) recruit 2 tobacco farms and 40 farm workers and randomly assign them to one of the two groups who will randomly receive one of the formulations; 4) collect urine samples and analyze them for nicotine and cotinine content; 5) test differences in nicotine exposure with and without the use of a barrier cream and between formulations; 6) assess barrier creams' acceptance/feasibility with workers. This pilot study may allow us to obtain preliminary data that would aid in future experimental intervention study design to evaluate the relative contributions and effectiveness of different types of strategies and protective technologies in reducing skin exposure to nicotine in tobacco farming, in addition to assessing the potential risk reduction of GTS. Our long-term goal is to use the research results to change the work practice and help prevent GTS in tobacco farmers and farm workers particularly migrant and seasonal farm workers and improve their health and safety. It is in accordance with the NIOSH new NORA agenda in this industry sector.